Altering the Natural History of Oligometastatic Prostate Cancer With Local Therapies: Reality Versus Illusion

In the first definitive treatise on low-volume metastatic cancerbyPhilipRubinandJerold Green,publishedin1968andentitledSolitary Metastases, the authors remark that “all too frequently, a solitarymetastasis is an illusion rather than a reality.” These authors faced similar fundamental questions regarding care for these patients with lowvolumemetastatic disease: “the clinician is faced with a choice between conservative or radical therapy. What type of surgery, radiotherapy or chemotherapy should be employed?” So what has changed in the past 50 years? In short, a lot! With subsequent medical advancements in staging—namely, imaging, and new metastasis-directed therapies such as stereotactic ablative radiotherapy—this formerly illusory oligometastatic state has again become an area of intense interest by cancer physicians. As originally hypothesized by Hellman and Weichselbaum, the oligometastatic state is juxtaposed at an intermediate position along the spectrum of cancer progression where local therapies may not only alter their natural history, but also cure men with this metastatic disease state (Fig 1). Preclinical data exist suggesting a unique biology of oligometastases in non–smallcell lung cancer (NSCLC) that has been mechanistically explained by microRNAmediated attenuation of prometastatic epithelial plasticity programs such as the epithelial-mesenchymal transition. Similarly, in NSCLC, we now have randomized clinical trial confirmation that local therapies canprolong theprogression-free survival of patients with three or fewer metastases after first-line systemic therapy for NSCLC. It is in this context of renewed excitement and knowledge regarding the oligometastatic state that the accompanying article by Clement and Sweeney reviews the current clinical standard of care and ongoingclinical trials formenwithhormonesensitive oligometastatic prostate cancer.We commend their efforts to summarize the existing retrospective data and catalogmany of the current clinical trials exploring the oligometastatic state in prostate cancer. To expound upon their work, we would like to highlight what we believe are key future outstanding clinical and biologic questions that will be important in the field of hormone-sensitive oligometastatic prostate cancer.